Neonatal Abstinence Syndrome (NAS) - Healthtrust .Neonatal Abstinence Syndrome (NAS) Dhara D. Shah,

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Text of Neonatal Abstinence Syndrome (NAS) - Healthtrust .Neonatal Abstinence Syndrome (NAS) Dhara D. Shah,

Neonatal Abstinence Syndrome (NAS)

Dhara D. Shah, PharmDPGY-1 Pharmacy Practice ResidentJanuary 31, 2018

Program for HealthTrust Members

Disclosures

This program may contain the mention of drugs or brands presented in a case study or comparative format using evidence-based research. Such examples are intended for educational and informational purposes and should not be perceived as an endorsement of any particular supplier, brand or drug.

The presenter has no financial relationships with any commercial interests pertinent to this presentation.

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Learning Objectives

1. Define the mechanism and clinical presentation of NAS

2. List advantages and limitations of assessment tools utilized for NAS

3. Recognize recommended treatment options for NAS

4. Discuss adjunctive therapies used for NAS

5. State important safety and efficacy parameters associated with the treatment options

3

Background

Withdrawal symptoms in newborns due to the combination in utero exposure and postnatal cessation

Sudden discontinuation of prolonged fetal exposure Incidence has increased significantly in the past decade

Proportionate with the increased use of opioids during pregnancy

Opioid use antepartum is the most common cause of NAS

Hudak ML, Tan RC. Pediatrics. 2012; 129: e540-60.Kocherlakota P. Pediatrics. 2014; 134(2): e546-61.Siu A, Robinson C. J Pediatr Pharmacol Ther. 2014; 19(3): 147-55.McQueen K, Murphy-Oikonen J. N Engl J Med. 2016; 375: 2468-79.

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Major Drugs of AbuseOpioids CNS Stimulants CNS Depressants Hallucinogens

Morphine Amphetamines Alcohol Indolealkylamines(e.g. LSD*)

Codeine Methylphenidate Barbiturates Phenylisopropylamines(e.g. MDMA**)

Methadone Phentermine Benzodiazepines Nitrates

OxyCODONE Cocaine Cannaboids Nitrous Oxide

HYDROmorphone Nicotine

HYDROcodone

TraMADol

Heroin

Buprenorphine

Hudak ML, Tan RC. Pediatrics. 2012; 129: e540-60.5

*LSD = lysergic acid diethylamide; **MDMA = 3,4-methylenedioxymethamphetamine; CNS = central nervous system

Risk of Withdrawal

Type and dose of opioid Timing and duration of exposure Maternal risk factors Placental opioid metabolism Genetic variables Neonatal conditions Environmental factors

Hudak ML, Tan RC. Pediatrics. 2012; 129: e540-60.Kocherlakota P. Pediatrics. 2014; 134(2): e546-61.Siu A, Robinson C. J Pediatr Pharmacol Ther. 2014; 19(3): 147-55.McQueen K, Murphy-Oikonen J. N Engl J Med. 2016; 375: 2468-79.

6

Outcomes of Maternal Opioid Use

Fetus Growth restriction Preterm labor Abnormal heart patterns Death

Newborn Low birth weight Preterm delivery Small head circumference Sleep myoclonus Child maltreatment Visual disturbances

McQueen K, Murphy-Oikonen J. N Engl J Med. 2016; 375: 2468-79.7

Outcomes of NAS

Increased risk of birth complications Admission to neonatal intensive care unit (NICU) Pharmacologic treatment Prolonged hospitalization Infant development Child-safety concerns

McQueen K, Murphy-Oikonen J. N Engl J Med. 2016; 375: 2468-79.8

Opioids in Pregnancy

Lower molecular weight Lipophilic substances Easily transferable across the placenta

Transmission increases with gestation Easily transferable across the blood-brain barrier Synthetic opioids cross the placenta more easily compared

to semisynthetic opioids

Hudak ML, Tan RC. Pediatrics. 2012; 129: e540-60.Siu A, Robinson C. J Pediatr Pharmacol Ther. 2014; 19(3): 147-55.9

Mechanism of Withdrawal

Hudak ML, Tan RC. Pediatrics. 2012; 129: e540-60.10

Fetal drug exposure

Tolerance: increased noradrenaline release

Abrupt discontinuation: increased release of

noradrenaline Autonomic and behavioral signs and symptoms

Withdrawal

Clinical Manifestations

Autonomic/vasomotor/respiratory Gastrointestinal CNS

Fever Projectile vomiting Tremors

Sweating Regurgitation High-pitched crying

Nasal stuffiness Loose/watery stools Sleep disturbances

Mottling Weight loss Increased muscle tone

Tachypnea with or without retractions Poor feeding/sucking

Frequent yawning/sneezing

Excessive sucking Irritability

Dehydration Seizures

Myoclonic jerks

Hudak ML, Tan RC. Pediatrics. 2012; 129: e540-60.Siu A, Robinson C. J Pediatr Pharmacol Ther. 2014; 19(3): 147-55.McQueen K, Murphy-Oikonen J. N Engl J Med. 2016; 375: 2468-79.

11

Timing of WithdrawalDrug Onset

Heroin 24 to 48 hours

Opioids 48 to 72 hours

Buprenorphine 36 to 60 hours

Barbiturates 1 to 14 days

Benzodiazepines Hours to weeks

SSRIs* 24 to 48 hours

Methamphetamines 24 hours

Cocaine 48 to 72 hours

Nicotine 24 to 48 hours

Alcohol 3 to 12 hours

Hudak ML, Tan RC. Pediatrics. 2012; 129: e540-60.Kocherlakota P. Pediatrics. 2014; 134(2): e546-61.Siu A, Robinson C. J Pediatr Pharmacol Ther. 2014; 19(3): 147-55.

12

*SSRI = selective serotonin reuptake inhibitor

Assessment

Determine severity of signs and symptoms Provide guidance for pharmacologic therapy Facilitate weaning Withdrawal scoring systems

Finnegan Scoring Toolo The Neonatal Abstinence Scoring System

Lipsitz Scoring Toolo The Neonatal Drug Withdrawal Scoring System

Modified Finnegan Scoring Toolo MOTHER NAS Scale

McQueen K, Murphy-Oikonen J. N Engl J Med. 2016; 375: 2468-79.13

Finnegan Scoring Tool

14 Finnegan LP, Connaughton JF Jr, Kron RE, et al. Addict Dis. 1975; 2: 141-58.Hudak ML, Tan RC. Pediatrics. 2012; 129: e540-60.

System Signs and Symptoms Score

Metabolic/vasomotor/respiratory

Sweating 1

Fever < 101F (39.3C)Fever > 101F (39.3C)

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Frequent yawning 1

Mottling 1

Nasal stuffiness 1

Sneezing (> 3 to 4 times/interval) 1

Nasal flaring 2

Respiratory rate > 60 breaths/minRespiratory rate > 60 breaths/min

with retractions

12

Finnegan Scoring Tool

15 Finnegan LP, Connaughton JF Jr, Kron RE, et al. Addict Dis. 1975; 2: 141-58.Hudak ML, Tan RC. Pediatrics. 2012; 129: e540-60.

System Signs and Symptoms Score

Gastrointestinal

Excessive sucking 1

Poor feeding 2

RegurgitationProjectile vomiting

23

Loose stoolsWatery stools

23

Finnegan Scoring ToolSystem Signs and Symptoms Score

Central Nervous

High pitched cryContinuous high pitched cry

23

Sleeps < 1 hour after feedingSleeps < 2 hours after feedingSleeps < 3 hours after feeding

321

Hyperactive Moro reflexMarkedly hyperactive Moro reflex

12

Mild tremors disturbedModerate-severe tremors disturbed

Mild tremors undisturbedModerate-severe tremors undisturbed

1234

Mild increased muscle tone 2

Excoriation (specific area) 1

Myoclonic jerks 3

Generalized convulsions 316 Finnegan LP, Connaughton JF Jr, Kron RE, et al. Addict Dis. 1975; 2: 141-58.

Hudak ML, Tan RC. Pediatrics. 2012; 129: e540-60.

Lipsitz Scoring ToolScoring Categories

Signs Score 0 Score 1 Score 2 Score 3

Tremors(muscle activity of limbs) Normal

Minimally increased when hungry or disturbed

Moderate/marked increase when undisturbed; stop

when fed or cuddled

Marked increase or continuouseven when undisturbed; going on to seizure-like movements

Irritability(excessive crying) None Slightly increased

Moderate to severe irritability when disturbed

or hungry

Marked irritability even when undisturbed

Reflexes Normal Increased Markedly increased

Stools Normal Explosive, but frequency 8/day Explosive; > 8/day

Muscle Tone Normal Increased Rigidity

Skin Abrasions No Redness of elbows, heels, pressure points when supineBreakdown of skin at

pressure points

Respiratory Rate (bpm) < 55 55 to 75 76 to 95

Repetitive Sneezing No Yes

Repetitive Yawning No Yes

Forceful Vomiting No Yes

Fever > 38C or >100.4F No Yes

Total Score

17

Withdrawal Scoring Systems

Tool (year) No. of Items Score Range Score for Treatment

Finnegan NeonatalAbstinence Scoring Tool

(1975)21 0 to 62

8 on three consecutive evaluations

Lipsitz Neonatal Drug Withdrawal Scoring

System (1975)11 0 to 20 4

MOTHER NAS Scale (2010) 19 0 to 42

9; rescore before initiation of drug

treatment

Finnegan Neonatal Abstinence Syndrome

Scale Short Form (2013)7 0 to 16 8

McQueen K, Murphy-Oikonen J. N Engl J Med. 2016; 375: 2468-79.18

Withdrawal Scoring SystemsTool (year) Comments

Finnegan Neonatal Abstinence Scoring Tool (1975)

- Most commonly utilized scoring tool- Lengthy/complex- Less practical- Internal consistency

Lipsitz Neonatal Drug Withdrawal Scoring System (1975)

- Simplistic/sensitive- Does not address reliability- No item definitions provided

MOTHER NAS Scale (2010)

- Modified version of Finnegan Scoring Tool- Proper instructions- Protocol for pharmacologic treatment- More practical- Internal consistency

Finnegan Neonatal Abstinence Syndrome Scale Short Form

(2013)

- Rapid assessment- Limited items- Strong correlation with original Finnegan Scoring Tool- Inadequate for rapidly escalating signs and symptoms- Requires further testing

McQueen K, Mu